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Dissection of Xenopus laevis Neural Crest for in vitro Explant Culture or in vivo Transplantation
Published on: March 4, 2014
Protein tyrosine phosphatase 4A3 (PTP4A3) is required for Xenopus laevis cranial neural crest migration in vivo
Selma Maacha1, Nathalie Planque2, Cécile Laurent1
1Institut Curie, Research Division, Orsay, France ; CNRS UMR3347, Orsay, France ; INSERM U1021, Orsay, France ; Université Paris Sud, Orsay, France.
Abstract:
Uveal melanoma is the most common intraocular malignancy in adults, representing between about 4% and 5% of all melanomas. High expression levels of Protein Tyrosine Phosphatase 4A3, a dual phosphatase, is highly predictive of metastasis development and PTP4A3 overexpression in uveal melanoma cells increases their in vitro migration and in vivo invasiveness. Melanocytes, including uveal melanocytes, are derived from the neural crest during embryonic development. We therefore suggested that PTP4A3 function in uveal melanoma metastasis may be related to an embryonic role during neural crest cell migration. We show that PTP4A3 plays a role in cephalic neural crest development in Xenopus laevis. PTP4A3 loss of function resulted in a reduction of neural crest territory, whilst gain of function experiments increased neural crest territory. Isochronic graft experiments demonstrated that PTP4A3-depleted neural crest explants are unable to migrate in host embryos. Pharmacological inhibition of PTP4A3 on dissected neural crest cells significantly reduced their migration velocity in vitro. Our results demonstrate that PTP4A3 is required for cephalic neural crest migration in vivo during embryonic development.
Insights
Protein Tyrosine Phosphatase 4A3 (PTP4A3) is crucial for neural crest cell migration during embryonic development. This finding may explain its role in uveal melanoma metastasis.
Area of Science:
- Developmental Biology
- Cancer Biology
- Cell Biology
Background:
- Uveal melanoma, the most common adult intraocular malignancy, shows high metastasis rates.
- Protein Tyrosine Phosphatase 4A3 (PTP4A3) overexpression correlates with uveal melanoma metastasis and invasiveness.
- Uveal melanocytes originate from the embryonic neural crest.
Purpose of the Study:
- To investigate the potential role of PTP4A3 in embryonic neural crest cell migration.
- To explore the link between PTP4A3's embryonic function and its role in uveal melanoma metastasis.
Main Methods:
- Utilized Xenopus laevis as a model organism for studying cephalic neural crest development.
- Employed loss-of-function and gain-of-function experiments to assess PTP4A3's impact on neural crest territory.
- Conducted isochronic graft experiments to evaluate neural crest cell migration.
- Performed in vitro migration assays on neural crest cells with pharmacological PTP4A3 inhibition.
Main Results:
- PTP4A3 loss of function reduced, while gain of function increased, cephalic neural crest territory in Xenopus.
- PTP4A3-depleted neural crest explants showed impaired migration in host embryos.
- In vitro inhibition of PTP4A3 significantly decreased neural crest cell migration velocity.
Conclusions:
- PTP4A3 is essential for cephalic neural crest migration in vivo.
- The embryonic role of PTP4A3 in neural crest migration provides a potential mechanism for its involvement in uveal melanoma metastasis.
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